Alanine methyl ester imine

North and coworkers have investigated application of Cu(II)/salen complex (405) and derivatives to enantioselective alkylation of alanine methyl ester imine (403) (Scheme 17.91) [128]. Numerous variations on the aryl rings of the salen ligand... 

Protonated imines are effective dienophiles. Thus in the reaction of methyl glyoxylate with the hydrochloride 127 of alanine methyl ester in the presence of cyclopentadiene, a mixture of hydrochlorides of the exo- and ewrfo-adducts 128-131 was formed (equation 69). The diastereomeric ratio of the exo-compounds was 83 1761. 

Enantiomerically pure aldehydes 287 were obtained by DIBAL reduction of the corresponding o-alanine methyl esters. Coupling with t-butyl glycinate quantitatively gave the ( )-imines 288 (Scheme 85). Peracid oxidation did not allow the isolation of oxaziridines 289 which spontaneously decomposed to give complex mixtures of products [156]. This was probably due to a deprotonation a to the ester group accompanied by cleavage of the weak N-O bond. Imines 290, derived from aldehydes 287 and P-alanine esters, could be indeed oxidised into stable oxaziridines 291 which were isolated as mixtures of two dia-stereoisomers (Scheme 86) [157]. 

Ethyl (bornylideneamino)acetate (2) and the imines of (-)-(lf ,2, 5 )-2-hydroxy-3-pinanone and glycine, alanine and norvaline methyl esters were particularly successful as Michael donors. The chiral azaallyl anions, derived from these imines by deprotonation with lithium diisopropylamide in THF at — 80 C, add to various a,/i-unsaturated esters with modest to high diastereoselectivity (see Section 1.5.2.4.2.2.5.). Thus, starting with the imine 2, (R1 = CH,) and ethyl ( )-2-butcnoate, the a,/i-dialkylated glutamate derivative 3 is obtained as a single diastercomer in 90% yield91-92. 

A-Phthaloyl-protected (S)-phenylalanine has been used as a ligand for rhodium in the formation of metallocarbenes from diazo compounds for C-H insertion reactions (Section D.1.2.2.3.2.). Ar-Sulfonyl-protected (S)-alanine and (S)-valine are efficient ligands for chiral Lewis acids used in the Diels-Alder reaction (Section D.1.6.1.1.1.3.). A -Sulfonyl-pro-tected (S)-phenylalanine methyl ester has been used for the enantioselective protonation of lactone enolates (Section D.2.I.). The terf-butyl ester of (S)-valine readily forms imines with carbonyl compounds which are used for the highly efficient alkylations of their azaenolates (Sections D.1.1.1.4.1D.1.5.2.4.). All these derivatives can be obtained by the standard methods described in Houben-Weyl3. 

The reductive alkylation of methyl pyruvate with and the t-butyl esters of amino acids using Pd/C catalyst leads to the formation of iminodicarboxylic acids such as 67 in selectivities of 29-75% d.e. depending on the amino acid and solvent used (hexane gave the best results). Hydrolysis of the t-butyl ester to the acid 68 followed by hypochlorite-promoted decarboxylation and imine hydrolysis leads to the formation of ( -alanine 69 in correspondingly high e.e.s278,281. The likely decarboxylation mechanism as far as the imine stage is shown in Scheme 65. 

In 1992, O Donnell succeeded in obtaining optically active a-methyl-a-amino acid derivatives 49 in a catalytic manner through the phase-transfer alkylation of p-chlorobenzaldehyde imine of alanine tert-butyl ester 48 with cinchonine-derived la as catalyst (see Scheme 4.16) [46]. Although the enantioselectivities are moderate, this study is the first example of preparing optically active a,a-dialkyl-a-amino acids by chiral phase-transfer catalysis. 

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